Chapter 1 Applied Chemical Technology Overview
Seldom do we encounter pure materials. Instead, many materials are mixtures made up of two or more chemically different substances. In order to isolate pure components of a mixture, chemists have developed a variety of techniques for the separation of one component from another, taking advantage of the differences in physical properties of the components. Recrystallization is one of the important laboratory processes frequently used for this.
Recrystallization is used to purify a solid substance at the temperature of the experiment. It is a basic purification technique based on different solubilities of solids. Insoluble impurities can be easily removed by filtration after dissolution of the solid that needs to be purified, while small amount of soluble impurities remains in the solution. Increasing the temperature produces a supersaturated solution which can be used to obtain crystals of the pure solid. When slowly cooling the solution down to room temperature, crystals form and crash out, with the impurities in the solution. Sometimes it is easier to conduct recrystallization using two solvents, one good solvent for the compound and one poor solvent.
Single-Solvent Approach.
A single-solvent recrystallization includes the following steps: selecting the solvent; dissolving the solid; cooling the solution; filtering and drying the crystals.
Selecting the Solvent
Choosing an appropriate solvent is the first step in a recrystallization. Water, hexane, methanol, and ethyl acetate are frequently used. Ideally, the solid is virtually insoluble in the solvent at room temperature, yet is completely soluble at higher temperatures at or near the boiling point of the solvent. To find a suitable solvent, it is necessary to test the solubility of the desired compound in different solvents. Test tubes and a rack, a test tube clamp, pipets and bulbs, a spatula, a beaker, and a hot plate are required, in addition to the compound, water, and the solvents.
Load a small amount of solid into a test tube, followed by adding about one milliliter of the test solvent. If the solid dissolves immediately at room temperature, the solvent is not suitable for recrystallization. Repeat this process with another test solvent using a clean test tube. If the solid does not dissolve, heat up the test tube using a hot water bath whose temperature is set at the boiling point of the test solvent. If the solid still remains, then this solvent is not good, either. Repeat with other solvents until the solid remains at room temperature, but dissolves in the solvent with the temperature - at the boiling point, indicating a good recrystallization solvent.
Dissolving the Solid
In the second step, the solid to be recrystallized is dissolved in the hot suitable solvent. Two Erlenmeyer flasks (one for the solvent and the other for the crystals), a hot plate, a disposable pipet and bulb, finger cots, and some boiling stones are needed in this step. Place two boiling stones in each flask to ensure smooth boiling during heating. A small amount of solvent is added to a flask containing the impure solid, and then the suspension in the flask is heated to the boiling point of the solvent until the complete dissolution of the solid. If the solid does not dissolve, add more hot solvent drop-wise continually until the solid is fully dissolved. A hot filtration is required if the solution contains visible solid impurities other than boiling stones. If the solution appears colored, the hot saturated solution is boiled for a short period of time with the addition of activated carbon to remove colored impurities, followed by a hot filtration to get rid of the activated carbon.
Cooling the Solution
Next, the solution is cooled for the desired compound to crystallize. A more pure solid precipitates out from the solution, leaving soluble impurities in the solvent. The Nobel laureate, the late Professor Robert Bums Woodward stated that crystallization is one of the most beautiful processes known, and no true chemist fails to experience a thrill when he brings a new form of matter into the crystalline state for the first time. In most cases, crystals grow as the solution cools down. Leave the solution undisturbed until the temperature decreases, and crystals begin to form on the bottom of the flask. Usually slower cooling leads to a more pure product. The size of crystals that form also depends on the cooling rate. Very small crystals tend to form upon rapid cooling and the impurities may also precipitate out of the solution along with the small crystals. Therefore, it is quite common to allow the solution to cool to room temperature first before cooling it further by setting the flask in an ice-water bath. Wait for the majority of crystals to form at room temperature and then place the flask in an ice-water bath.
However, sometimes crystallization needs to be induced by nucleation. One method is to scratch the flask with a glass rod at the air-solvent meniscus. The scratch increases the surface area of the glass, resulting in a roughened surface on which the solid can nucleate and crystallize. Another technique is to add a small crystal of the desired pure solid as the “seed” into the cooled solution if such a crystal is available. The “seed” crystal serves as the nucleating site for the crystal to grow. Make sure that the solution is cool; otherwise, the added small crystal would dissolve.
If there are no crystals falling out of the solution, it is possible that too much solvent has been used. The solution should be concentrated further by allowing some of the solvent to evaporate. If crystals do not immediately form, reheat and then cool the solution.
Filtering and Drying the Crystals
After crystals have formed, it is time to separate them from the solution. Vacuum filtration is frequently used to isolate and dry the purified solid, sometimes washing the purified solid with chilled solvent. Use the smallest possible amount of cold solvent when washing the product to avoid dissolving some of the sample.
Vacuum is supplied by a pump and applied to the filter flask through a rubber tubing. Add filter paper to the funnel which is placed on the filter vacuum adapter in the neck of the filter flask. Use a small amount of the recrystallization solvent to moisten the filter paper and then turn on the pump. Pour and transfer the crystals and solution to the center of the filter paper. Add cold solvent to the flask and swirl the remaining crystals into the funnel.
Once the liquid is all sucked through, turn off the pump to release the vacuum. Then add a small amount of cold, clean solvent to wash the crystals and apply a gentle suction to allow the fresh solvent passing through the crystals at a slower rate. Note that suction should not be applied while washing. In order to dry the crystals as thoroughly as possible, full suction is applied for a few minutes. Drying the product via vacuum filtration should remove much of the solvent. Depending on the volatility of the solvent, sometimes open-air drying is used as well.
After filtering and drying, the final step is to remove the crystals from the filter fiinnel. Use a spatula to transfer the crystals to a watch glass. Physically separate any remaining boiling stones from the crystals in this step. In some cases, the recrystallization process is repeated to further purify the substance.
Two-Solvent Approach
When it is not possible to find a single recrystallization solvent, a two-solvent recrystallization method has to be used. In such a process, the primary solvent (Solvent A) can dissolve the desired compound at the boiling point, and the second solvent (Solvent B) should induce crystallization when added to the saturated solution of the compound in Solvent A. The same four steps are involved in a two-solvent recrystallization: selecting the solvents; dissolving the solid; cooling the solution; filtering and drying the crystals.
Selecting the Solvents
Similar to the single-solvent approach, the first step is also to select suitable solvents. As mentioned above, two solvents are needed, with one being a very good solvent for the compound and the other extremely poor at room temperature. And these two solvents must be miscible.
A glass plate, a spatula, and several clean Pasteur pipets and bulbs are needed in this step along with a range of candidate solvents and the compound to be purified. To select the solvents, only a small amount of solid compound is needed. On a glass plate a tiny amount of the compound is placed, then about four centimeters away another sample is added. In a similar fashion place more solid samples on the glass plate until there are enough samples for the number of solvents to be chosen from. Select solvents with different polarity such as water, methanol, ethyl acetate, and hexane. Take three or four drops of one test solvent and add them to one solid sample. And repeat this process for the remaining solvents. Check the solubility results and evaluate whether the compound dissolves completely, partially, or not at all. Again, the perfect combination of solvents means that one solvent (Solvent A) easily dissolves the compound and the second solvent (Solvent B) does not dissolve the compound.
Dissolving the Solid
In this recrystallization approach, the two solvents A and B should also be hot. Add each solvent in an Erlenmeyer flask along with boiling stones. Then heat up the solvents until near their respective boiling points. Load the impure compound in a tared test tube that is no more than one quarter full of solid.
Add the first recrystallization Solvent A, to dissolve the crystals. Add just enough hot Solvent A with a Pasteur pipet to the test tube that contains the compound. During additions of Solvent A, heat and shake the test tube to help dissolve the compound. Minimum amount of hot Solvent A should be used and the volume of Solvent A should not exceed one third of that of the test tube. The second Solvent B, is then added to the solution until the solution becomes cloudy. Generally, no more than twenty drops of Solvent B is needed.
Alternatively, the solid can be suspended in the second Solvent B. Then hot Solvent A is added until the solid just dissolves.
The last two steps (cooling the solution and filtering and drying the crystals) in two-solvent recrystallization are similar to those in the single-solvent method, although here to wash the crystals in the last step, use a mixture of the solvent system in about the same ratio used to obtain a saturated solution.